Human monocytes release elevated levels of interleukin-1 (IL-1) and prostaglandin E2 (PGE2) when stimulated with bacterial lipopolysaccharide (LPS). These soluble mediators possess certain proinflammatory, immunosuppressive and bone resorbing characteristics and may be important in the pathogenesis of periodontitis. Recently, we have examined the capacity of human monocytes to release these products following treatment with several LPS preparations isolated from suspected periodontal pathogens. LPS preparations promoted PGE2 and IL-1 release with the following relative potencies: Wolinella recta greater than or equal to Salmonella typhimurium greater than Actinobacillus actinomycetemcomintans greater than Bacteroides intermedius greater than B. gingivalis. In a preliminary clinical study, monocytes were isolated from dental patients with generalized severe adult periodontitis or age matched patients with little or no attachment loss. Patients with severe periodontitis released 2-3 fold more PGE2 than control patients when cells were treated with LPS preparations isolated from Salmonella typhimurium, Bacteroides intermedius, B. gingivalis and Actinobacillus actinomycetemcomintans. Surprisingly, IL-1 release was similar for severe periodontitis patients and controls. These findings suggest that LPS-mediated secretion of PGE2 from monocytes may be related to the susceptibility of an individual to periodontitis. Recently, we have determined that gamma interferon, a product of activated T lymphocytes, can specifically potentiate PGE2 and IL-1 release from monocytes treated with Bacteroides LPS but not Salmonella. We propose to examine monocyte secretory response to highly defined preparations of LPS, with or without gamma interferon, in patients with either severe periodontitis or no significant attachment loss. Secretion of PGE2 and IL-1 will be determined prior to the initiation of periodontal therapy, after initial therapy, immediately following surgical therapy and 4 months after the completion of all therapy. PGE2 will be quantitated by GC-MS and IL-1 will be quantitated by RIA. In addition, we will assess monocyte secretory responses for cells isolated from a limited number of patients with localized severe periodontitis. We hope to establish that LPS-mediated PGE2 release from monocytes is an inherent response which is not affected by periodontal therapy.